Biomolecular events in cancer revealed by attractor metagenes

PLoS Comput Biol. 2013;9(2):e1002920. doi: 10.1371/journal.pcbi.1002920. Epub 2013 Feb 21.

Abstract

Mining gene expression profiles has proven valuable for identifying signatures serving as surrogates of cancer phenotypes. However, the similarities of such signatures across different cancer types have not been strong enough to conclude that they represent a universal biological mechanism shared among multiple cancer types. Here we present a computational method for generating signatures using an iterative process that converges to one of several precise attractors defining signatures representing biomolecular events, such as cell transdifferentiation or the presence of an amplicon. By analyzing rich gene expression datasets from different cancer types, we identified several such biomolecular events, some of which are universally present in all tested cancer types in nearly identical form. Although the method is unsupervised, we show that it often leads to attractors with strong phenotypic associations. We present several such multi-cancer attractors, focusing on three that are prominent and sharply defined in all cases: a mesenchymal transition attractor strongly associated with tumor stage, a mitotic chromosomal instability attractor strongly associated with tumor grade, and a lymphocyte-specific attractor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Data Mining
  • Databases, Genetic
  • Epithelial-Mesenchymal Transition
  • Gene Expression Profiling / methods
  • Genome / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Kinetochores
  • Mitosis / genetics
  • Models, Biological*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oncogenes
  • Phenotype
  • Prognosis

Grant support

This work was funded by Columbia University's unrestricted-purpose allocation of inventor's research of royalties resulting from intellectual property totally unrelated to the work described in this paper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.